- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2009-11-25 12:09:03+13:00
- Desc:
- Added images in ai and svg fomrat, removed non pub med reference
- Permanent Source URI:
- https://models.cellml.org/workspace/cortassa_aon_winslow_orourke_2004/rawfile/818d1babc176006aec3a7bbfccaaab6f2fa71289/cortassa_aon_winslow_orourke_2004.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : cortassa_model_2004.xml
CREATED : 28th September 2004
LAST MODIFIED : 28th September 2004
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Cortassa et al.'s 2004 mathematical model of a mitochondrial oscillator which is dependent on Reactive Oxygen Species.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="cortassa_aon_marban_winslow_orourke_2004_version01" name="cortassa_aon_marban_winslow_orourke_2004_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling Mitochondrial Energy Metabolism</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model has been checked in both OpenCell and COR and the units are consistent. Unfortunately the model will not integrate at the moment. We are working with the model author to complete the curation of this model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In order to be able to rapidly adapt to environmental changes, biological systems require dynamic control systems which function near the edge of instability. Dynamic control can be in the form of oscillations, such as cytosolic calcium concentration oscillations(eg Sneyd et al., Modelling the Control of Calcium Oscillations by Membrane Fluxes, 2004), electrical pacemaker cells (eg Lovell et al., A Gradient Model Of Cardiac Pacemaker Myocytes, 2004), and secretion of insulin from pancreatic islets (eg Keener, A Model of Diffusion Induced Oscillatory Insulin Secretion in Pancreatic Beta Cells, 2001)
</para>
<para>
Oscillations in energy metabolism also occur for example in mitochondria, there are oscillations in the transmembrane ionic currents. Experimental data have shown that oscillation of the mitochondrial energy state occur as a consequence of the interactions between mitochondrial reactive oxygen species (ROS) production and the ROS scavenging systems of the cell. In the current study, Cortassa et al. use this experimental data as the basis for their mathematical model, which incorporates mitochondrial ROS synthesis, ROS scavenging, and ion channels within the mitochondrial membrane (see Figure 1 below). This mathematical model of a mitochondrial oscillator is embedded within a previously published model of cardiac mitochondrial energetics (see Cortassa et al. Modelling Mitochondrial Energy Metabolism, 2003, and also see Figure 2 below for more details)
</para>
<para>
Model simulations have generated data which match experimental results. Furthermore, the model simulations also demonstrate that the period of the mitochondrial oscillator can be modulated over a wide range of timescales, from milliseconds to hours, by altering a single parameter, the rate of ROS scavenging by the enzyme superoxide dismutase.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
A Mitochondrial Oscillator Dependent on Reactive Oxygen Species, Sonia Cortassa, Miguel A. Aon, Raimond L. Winslow, and Brian O'Rourke, 2004, <emphasis>Biophysical Journal</emphasis>, 87, 2060-2073.<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15345581&dopt=Abstract">PubMed ID: 15345581</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="cortassa_2004a.png"/>
</imageobject>
</mediaobject>
<caption>Figure 1. A schematic diagram of mitochondrial energetics coupled to ROS production, transport, and scavenging. These processes are described by the equations in Cortassa et al.'s 2004 mathematical model</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="cortassa_2004b.png"/>
</imageobject>
</mediaobject>
<caption>Figure 2. A schematic diagram of the reactions used in the model of the glycogenolysis pathway in skeletal muscle.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="per_millimolar">
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</units>
<units name="millimolar_per_volt">
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<units name="flux">
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<unit units="second"/>
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<unit units="coulomb"/>
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<units name="coulomb_per_mole">
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</units>
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
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<rdf:RDF>
<rdf:Description rdf:about="#ADP_m">
<dc:title>ADP_m</dc:title>
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mitochondrial adenosine diphosphate
</dcterms:alternative>
</rdf:Description>
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</apply>
</apply>
</math>
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<rdf:RDF>
<rdf:Description rdf:about="#NADH">
<dc:title>NADH</dc:title>
<dcterms:alternative>
nicotinamide adenine dinucleotide
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="NADH" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_O2"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<variable units="second" public_interface="in" name="time"/>
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<apply>
<eq/>
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<diff/>
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<ci>time</ci>
</bvar>
<ci>NADH</ci>
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<apply>
<plus/>
<apply>
<minus/>
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</apply>
<ci>V_IDH</ci>
<ci>V_KGDH</ci>
<ci>V_MDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ISOC" name="ISOC">
<rdf:RDF>
<rdf:Description rdf:about="#ISOC">
<dc:title>ISOC</dc:title>
<dcterms:alternative>isocitrate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ISOC" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_ACO"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
</bvar>
<ci>ISOC</ci>
</apply>
<apply>
<minus/>
<ci>V_ACO</ci>
<ci>V_IDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="alpha_KG" name="alpha_KG">
<rdf:RDF>
<rdf:Description rdf:about="#alpha_KG">
<dc:title>alpha_KG</dc:title>
<dcterms:alternative>alpha-ketoglutarate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="alpha_KG" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_AAT"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>alpha_KG</ci>
</apply>
<apply>
<plus/>
<ci>V_AAT</ci>
<ci>V_IDH</ci>
<apply>
<minus/>
<ci>V_KGDH</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="SCoA" name="SCoA">
<rdf:RDF>
<rdf:Description rdf:about="#SCoA">
<dc:title>SCoA</dc:title>
<dcterms:alternative>succinyl CoA</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="SCoA" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_SL"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
</bvar>
<ci>SCoA</ci>
</apply>
<apply>
<minus/>
<ci>V_KGDH</ci>
<ci>V_SL</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Suc" name="Suc">
<rdf:RDF>
<rdf:Description rdf:about="#Suc">
<dc:title>Suc</dc:title>
<dcterms:alternative>succinate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Suc" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_SL"/>
<variable units="flux" public_interface="in" name="V_SDH"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
</bvar>
<ci>Suc</ci>
</apply>
<apply>
<minus/>
<ci>V_SL</ci>
<ci>V_SDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="FUM" name="FUM">
<rdf:RDF>
<rdf:Description rdf:about="#FUM">
<dc:title>FUM</dc:title>
<dcterms:alternative>fumarate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="FUM" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_SDH"/>
<variable units="flux" public_interface="in" name="V_FH"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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<ci>FUM</ci>
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<apply>
<minus/>
<ci>V_SDH</ci>
<ci>V_FH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="MAL" name="MAL">
<rdf:RDF>
<rdf:Description rdf:about="#MAL">
<dc:title>MAL</dc:title>
<dcterms:alternative>malate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="MAL" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_FH"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
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<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MAL</ci>
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<apply>
<minus/>
<ci>V_FH</ci>
<ci>V_MDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="OAA" name="OAA">
<rdf:RDF>
<rdf:Description rdf:about="#OAA">
<dc:title>OAA</dc:title>
<dcterms:alternative>oxaloacetate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="OAA" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<variable units="flux" public_interface="in" name="V_CS"/>
<variable units="flux" public_interface="in" name="V_AAT"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<ci>OAA</ci>
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</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ASP" name="ASP">
<rdf:RDF>
<rdf:Description rdf:about="#ASP">
<dc:title>ASP</dc:title>
<dcterms:alternative>aspartate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
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<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
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<ci>ASP</ci>
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<apply>
<minus/>
<ci>V_AAT</ci>
<ci>V_C_ASP</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca_m" name="Ca_m">
<rdf:RDF>
<rdf:Description rdf:about="#Ca_m">
<dc:title>Ca_m</dc:title>
<dcterms:alternative>mitochondrial calcium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Ca_m" initial_value="0.01"/>
<variable units="dimensionless" name="f" initial_value="0.0003"/>
<variable units="flux" public_interface="in" name="V_uni"/>
<variable units="flux" public_interface="in" name="V_NaCa"/>
<variable units="second" public_interface="in" name="time"/>
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</bvar>
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<minus/>
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<ci>V_NaCa</ci>
</apply>
</apply>
</apply>
</math>
</component>
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<rdf:RDF>
<rdf:Description rdf:about="#Ca_i">
<dc:title>Ca_i</dc:title>
<dcterms:alternative>cytosolic calcium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Ca_i"/>
<variable units="second" name="stim_start" initial_value="0"/>
<variable units="second" name="stim_end" initial_value="10000"/>
<variable units="second" name="stim_period"/>
<variable units="second" name="stim_duration" initial_value="0.4"/>
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<variable units="second" public_interface="in" name="time"/>
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<piece>
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</apply>
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</piece>
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</math>
</component>
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<rdf:RDF>
<rdf:Description rdf:about="#Na_i">
<dc:title>Na_i</dc:title>
<dcterms:alternative>cytosolic sodium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
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</component>
<component cmeta:id="ATP_i" name="ATP_i">
<rdf:RDF>
<rdf:Description rdf:about="#ATP_i">
<dc:title>ATP_i</dc:title>
<dcterms:alternative>
cytosolic adenosine triphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
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</component>
<component cmeta:id="ATP_m" name="ATP_m">
<rdf:RDF>
<rdf:Description rdf:about="#ATP_m">
<dc:title>ATP_m</dc:title>
<dcterms:alternative>
mitochondrial adenosine triphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ATP_m"/>
<variable units="millimolar" name="Cm" initial_value="15.0"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ATP_m</ci>
<apply>
<minus/>
<ci>Cm</ci>
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</math>
</component>
<component cmeta:id="ADP_i" name="ADP_i">
<rdf:RDF>
<rdf:Description rdf:about="#ADP_i">
<dc:title>ADP_i</dc:title>
<dcterms:alternative>
cytosolic adenosine diphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ADP_i"/>
<variable units="millimolar" name="pulse_value" initial_value="0.15"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<piece>
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<apply>
<and/>
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<ci>time</ci>
<cn cellml:units="second">100</cn>
</apply>
<apply>
<lt/>
<ci>time</ci>
<cn cellml:units="second">300</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn cellml:units="millimolar">0.05</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component cmeta:id="GLU" name="GLU">
<rdf:RDF>
<rdf:Description rdf:about="#GLU">
<dc:title>GLU</dc:title>
<dcterms:alternative>glutamate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="GLU" initial_value="20"/>
</component>
<component cmeta:id="Mg" name="Mg">
<rdf:RDF>
<rdf:Description rdf:about="#Mg">
<dc:title>Mg</dc:title>
<dcterms:alternative>magnesium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Mg" initial_value="0.4"/>
</component>
<component cmeta:id="H" name="H">
<rdf:RDF>
<rdf:Description rdf:about="#H">
<dc:title>H</dc:title>
<dcterms:alternative>proton</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="H" initial_value="2.5E-5"/>
</component>
<component cmeta:id="Pi" name="Pi">
<rdf:RDF>
<rdf:Description rdf:about="#Pi">
<dc:title>Pi</dc:title>
<dcterms:alternative>inorganic phosphate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Pi" initial_value="20.0"/>
</component>
<component cmeta:id="CoA" name="CoA">
<rdf:RDF>
<rdf:Description rdf:about="#CoA">
<dc:title>CoA</dc:title>
<dcterms:alternative>Coenzyme A</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="CoA" initial_value="0.02"/>
</component>
<component cmeta:id="AcCoA" name="AcCoA">
<rdf:RDF>
<rdf:Description rdf:about="#AcCoA">
<dc:title>AcCoA</dc:title>
<dcterms:alternative>acetyl Coenzyme A</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="AcCoA" initial_value="0.0002"/>
</component>
<component cmeta:id="FAD" name="FAD">
<rdf:RDF>
<rdf:Description rdf:about="#FAD">
<dc:title>FAD</dc:title>
<dcterms:alternative>
flavin adenine dinucleotide (oxidised)
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="FAD" initial_value="0.01"/>
</component>
<component cmeta:id="FADH2" name="FADH2">
<rdf:RDF>
<rdf:Description rdf:about="#FADH2">
<dc:title>FADH2</dc:title>
<dcterms:alternative>
flavin adenine dinucleotide (reduced)
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="FADH2" initial_value="1.24"/>
</component>
<component cmeta:id="NAD" name="NAD">
<rdf:RDF>
<rdf:Description rdf:about="#NAD">
<dc:title>NAD</dc:title>
<dcterms:alternative>
charged nicotinamide adenine dinucleotide
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="NAD"/>
<variable units="millimolar" public_interface="in" name="NADH"/>
<variable units="millimolar" name="C_PN" initial_value="10.0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="NAD_calculation">
<eq/>
<ci> NAD </ci>
<apply>
<minus/>
<ci> C_PN </ci>
<ci> NADH </ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="NADPH" name="NADPH">
<rdf:RDF>
<rdf:Description rdf:about="#NADPH">
<dc:title>NADPH</dc:title>
<dcterms:alternative>
reduced nicotinamide adenine dinucleotide phosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="NADPH" initial_value="1.0"/>
</component>
<component name="O2_m" cmeta:id="O2_m">
<rdf:RDF>
<rdf:Description rdf:about="#O2_m">
<dc:title>O2_m</dc:title>
<dcterms:alternative>mitochondrial superoxide radical</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="O2_m" initial_value="0.01"/>
<variable units="dimensionless" name="shunt" initial_value="0.05"/>
<variable units="flux" public_interface="in" name="V_O2"/>
<variable units="flux" public_interface="in" name="VTr_ROS"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> O2_m </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> shunt </ci>
<ci> V_O2 </ci>
</apply>
<ci> VTr_ROS </ci>
</apply>
</apply>
</math>
</component>
<component name="O2_i" cmeta:id="O2_i">
<rdf:RDF>
<rdf:Description rdf:about="#O2_i">
<dc:title>O2_i</dc:title>
<dcterms:alternative>cytoplasmic superoxide radical</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="O2_i" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_SOD"/>
<variable units="flux" public_interface="in" name="VTr_ROS"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> O2_i </ci>
</apply>
<apply>
<minus/>
<ci> VTr_ROS </ci>
<ci> V_SOD </ci>
</apply>
</apply>
</math>
</component>
<component name="H2O2" cmeta:id="H2O2">
<rdf:RDF>
<rdf:Description rdf:about="#H2O2">
<dc:title>H2O2</dc:title>
<dcterms:alternative>hydrogen peroxide</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="H2O2" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_SOD"/>
<variable units="flux" public_interface="in" name="V_CAT"/>
<variable units="flux" public_interface="in" name="V_GPX"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> H2O2 </ci>
</apply>
<apply>
<minus/>
<ci> V_SOD </ci>
<apply>
<plus/>
<ci> V_CAT </ci>
<ci> V_GPX </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="GSH" cmeta:id="GSH">
<rdf:RDF>
<rdf:Description rdf:about="#GSH">
<dc:title>GSH</dc:title>
<dcterms:alternative>glutathione</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="GSH" initial_value="0.01"/>
<variable units="flux" public_interface="in" name="V_GR"/>
<variable units="flux" public_interface="in" name="V_GPX"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> GSH </ci>
</apply>
<apply>
<minus/>
<ci> V_GR </ci>
<ci> V_GPX </ci>
</apply>
</apply>
</math>
</component>
<component name="GSSG" cmeta:id="GSSG">
<rdf:RDF>
<rdf:Description rdf:about="#GSSG">
<dc:title>GSSG</dc:title>
<dcterms:alternative>glutathione disulphide</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="GSSG"/>
<variable units="millimolar" name="GT" initial_value="1.0"/>
<variable units="millimolar" public_interface="in" name="GSH"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> GSSG </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<apply>
<minus/>
<ci> GT </ci>
<ci> GSH </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="CIT" name="CIT">
<rdf:RDF>
<rdf:Description rdf:about="#CIT">
<dc:title>CIT</dc:title>
<dcterms:alternative>citric acid</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="CIT"/>
<variable units="millimolar" public_interface="in" name="ISOC"/>
<variable units="millimolar" public_interface="in" name="alpha_KG"/>
<variable units="millimolar" public_interface="in" name="SCoA"/>
<variable units="millimolar" public_interface="in" name="Suc"/>
<variable units="millimolar" public_interface="in" name="FUM"/>
<variable units="millimolar" public_interface="in" name="MAL"/>
<variable units="millimolar" public_interface="in" name="OAA"/>
<variable units="millimolar" name="C_Kint" initial_value="1.0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="CIT_calculation">
<eq/>
<ci> CIT </ci>
<apply>
<minus/>
<ci> C_Kint </ci>
<apply>
<plus/>
<ci> ISOC </ci>
<ci> alpha_KG </ci>
<ci> SCoA </ci>
<ci> Suc </ci>
<ci> FUM </ci>
<ci> MAL </ci>
<ci> OAA </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="mitochondrial_membrane">
<variable units="volt" public_interface="out" name="delta_psi_m" initial_value="0.01"/>
<variable units="volt_coulomb_per_mole_kelvin" public_interface="out" name="R" initial_value="8.315"/>
<variable units="kelvin" public_interface="out" name="T" initial_value="310.16"/>
<variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96480"/>
<variable units="millimolar_per_volt" name="C_mito" initial_value="1.812"/>
<variable units="flux" public_interface="in" name="V_He"/>
<variable units="flux" public_interface="in" name="V_He_F"/>
<variable units="flux" public_interface="in" name="V_Hu"/>
<variable units="flux" public_interface="in" name="V_ANT"/>
<variable units="flux" public_interface="in" name="V_Hleak"/>
<variable units="flux" public_interface="in" name="V_NaCa"/>
<variable units="flux" public_interface="in" name="V_uni"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="delta_psi_m_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> delta_psi_m </ci>
</apply>
<apply>
<divide/>
<apply>
<plus/>
<ci> V_He </ci>
<ci> V_He_F </ci>
<apply>
<minus/>
<apply>
<plus/>
<ci> V_Hu </ci>
<ci> V_ANT </ci>
<ci> V_Hleak </ci>
<ci> V_NaCa </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> V_uni </ci>
</apply>
</apply>
</apply>
</apply>
<ci> C_mito </ci>
</apply>
</apply>
</math>
</component>
<component name="V_CS">
<variable units="flux" public_interface="out" name="V_CS"/>
<variable units="millimolar" public_interface="in" name="OAA"/>
<variable units="millimolar" public_interface="in" name="AcCoA"/>
<variable units="millimolar" name="Km_AcCoA" initial_value="1.26E-2"/>
<variable units="millimolar" name="Km_OAA" initial_value="6.4E-4"/>
<variable units="first_order_rate_constant" name="Kcat_CS" initial_value="3.2"/>
<variable units="millimolar" name="ET_CS" initial_value="0.4"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_CS_calculation">
<eq/>
<ci> V_CS </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Kcat_CS </ci>
<ci> ET_CS </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Km_AcCoA </ci>
<ci> AcCoA </ci>
</apply>
<apply>
<divide/>
<ci> Km_OAA </ci>
<ci> OAA </ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_AcCoA </ci>
<ci> AcCoA </ci>
</apply>
<apply>
<divide/>
<ci> Km_OAA </ci>
<ci> OAA </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_ACO">
<variable units="flux" public_interface="out" name="V_ACO"/>
<variable units="millimolar" public_interface="in" name="CIT"/>
<variable units="millimolar" public_interface="in" name="ISOC"/>
<variable units="first_order_rate_constant" name="Kf_ACO" initial_value="12.5"/>
<variable units="dimensionless" name="KE_ACO" initial_value="2.22"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_ACO_calculation">
<eq/>
<ci> V_ACO </ci>
<apply>
<times/>
<ci> Kf_ACO </ci>
<apply>
<minus/>
<ci> CIT </ci>
<apply>
<divide/>
<ci> ISOC </ci>
<ci> KE_ACO </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_IDH">
<variable units="flux" public_interface="out" name="V_IDH"/>
<variable units="millimolar" public_interface="in" name="NAD"/>
<variable units="millimolar" public_interface="in" name="NADH"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<variable units="micromolar" public_interface="in" name="Ca_m"/>
<variable units="millimolar" public_interface="in" name="H"/>
<variable units="millimolar" public_interface="in" name="ISOC"/>
<variable units="millimolar" name="Kh_1" initial_value="8.1E-5"/>
<variable units="millimolar" name="Kh_2" initial_value="5.98E-5"/>
<variable units="millimolar" name="Km_ISOC" initial_value="1.52"/>
<variable units="millimolar" name="Ka_ADP" initial_value="6.2E-2"/>
<variable units="micromolar" name="Ka_Ca" initial_value="1.41"/>
<variable units="millimolar" name="Km_NAD" initial_value="0.923"/>
<variable units="millimolar" name="Ki_NADH" initial_value="0.19"/>
<variable units="first_order_rate_constant" name="Kcat_IDH" initial_value="1.94"/>
<variable units="millimolar" name="ET_IDH" initial_value="0.109"/>
<variable units="dimensionless" name="ni" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_IDH_calculation">
<eq/>
<ci> V_IDH </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Kcat_IDH </ci>
<ci> ET_IDH </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> H </ci>
<ci> Kh_1 </ci>
</apply>
<apply>
<divide/>
<ci> Kh_2 </ci>
<ci> H </ci>
</apply>
<apply>
<divide/>
<apply>
<power/>
<apply>
<divide/>
<ci> Km_ISOC </ci>
<ci> ISOC </ci>
</apply>
<ci> ni </ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> ADP_m </ci>
<ci> Ka_ADP </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_m </ci>
<ci> Ka_Ca </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_NAD </ci>
<ci> NAD </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> NADH </ci>
<ci> Ki_NADH </ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<power/>
<apply>
<divide/>
<ci> Km_ISOC </ci>
<ci> ISOC </ci>
</apply>
<ci> ni </ci>
</apply>
<apply>
<divide/>
<ci> Km_NAD </ci>
<ci> NAD </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> NADH </ci>
<ci> Ki_NADH </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> ADP_m </ci>
<ci> Ka_ADP </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_m </ci>
<ci> Ka_Ca </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_KGDH">
<variable units="flux" public_interface="out" name="V_KGDH"/>
<variable units="millimolar" public_interface="in" name="Mg"/>
<variable units="micromolar" public_interface="in" name="Ca_m"/>
<variable units="millimolar" public_interface="in" name="NAD"/>
<variable units="millimolar" public_interface="in" name="alpha_KG"/>
<variable units="millimolar" name="Km_alpha_KG" initial_value="1.94"/>
<variable units="first_order_rate_constant" name="Kcat_KGDH" initial_value="0.15"/>
<variable units="millimolar" name="ET_KGDH" initial_value="0.5"/>
<variable units="millimolar" name="Kd_Mg" initial_value="0.0308"/>
<variable units="micromolar" name="Kd_Ca" initial_value="1.27"/>
<variable units="dimensionless" name="n_alpha_KG" initial_value="1.2"/>
<variable units="millimolar" name="Km_NAD" initial_value="38.7"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_KGDH_calculation">
<eq/>
<ci> V_KGDH </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Kcat_KGDH </ci>
<ci> ET_KGDH </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<apply>
<power/>
<apply>
<divide/>
<ci> Km_alpha_KG </ci>
<ci> alpha_KG </ci>
</apply>
<ci> n_alpha_KG </ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Mg </ci>
<ci> Kd_Mg </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_m </ci>
<ci> Kd_Ca </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<divide/>
<ci> Km_NAD </ci>
<ci> NAD </ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Mg </ci>
<ci> Kd_Mg </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_m </ci>
<ci> Kd_Ca </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_SL">
<variable units="flux" public_interface="out" name="V_SL"/>
<variable units="millimolar" public_interface="in" name="SCoA"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<variable units="millimolar" public_interface="in" name="Suc"/>
<variable units="millimolar" public_interface="in" name="ATP_m"/>
<variable units="millimolar" public_interface="in" name="CoA"/>
<variable units="second_order_rate_constant" name="kf_SL" initial_value="0.127"/>
<variable units="millimolar" name="Ke_SL" initial_value="3.115"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_SL_calculation">
<eq/>
<ci> V_SL </ci>
<apply>
<times/>
<ci> kf_SL </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> SCoA </ci>
<ci> ADP_m </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> Suc </ci>
<ci> ATP_m </ci>
<ci> CoA </ci>
</apply>
<ci> Ke_SL </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_SDH">
<variable units="flux" public_interface="out" name="V_SDH"/>
<variable units="millimolar" public_interface="in" name="Suc"/>
<variable units="millimolar" public_interface="in" name="FUM"/>
<variable units="millimolar" public_interface="in" name="OAA"/>
<variable units="millimolar" name="Kisdh_OAA" initial_value="0.15"/>
<variable units="first_order_rate_constant" name="Kcat_SDH" initial_value="1.0"/>
<variable units="millimolar" name="ET_SDH" initial_value="0.5"/>
<variable units="millimolar" name="Km_Suc" initial_value="3.0E-2"/>
<variable units="millimolar" name="Ki_FUM" initial_value="1.3"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_SDH_calculation">
<eq/>
<ci> V_SDH </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Kcat_SDH </ci>
<ci> ET_SDH </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_Suc </ci>
<ci> Suc </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> OAA </ci>
<ci> Kisdh_OAA </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> FUM </ci>
<ci> Ki_FUM </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_MDH">
<variable units="flux" public_interface="out" name="V_MDH"/>
<variable units="millimolar" public_interface="in" name="MAL"/>
<variable units="millimolar" public_interface="in" name="OAA"/>
<variable units="millimolar" public_interface="in" name="NAD"/>
<variable units="millimolar" public_interface="in" name="H"/>
<variable units="millimolar" name="Km_MAL" initial_value="1.493"/>
<variable units="first_order_rate_constant" name="Kcat_MDH" initial_value="2.775E1"/>
<variable units="millimolar" name="ET_MDH" initial_value="0.154"/>
<variable units="millimolar" name="Ki_OAA" initial_value="3.1E-3"/>
<variable units="dimensionless" name="fh_a"/>
<variable units="dimensionless" name="fh_i"/>
<variable units="millimolar" name="Km_NAD" initial_value="0.2244"/>
<variable units="millimolar" name="kh1" initial_value="1.13E-5"/>
<variable units="millimolar" name="kh2" initial_value="26.7"/>
<variable units="millimolar" name="kh3" initial_value="6.68E-9"/>
<variable units="millimolar" name="kh4" initial_value="5.62E-6"/>
<variable units="dimensionless" name="k_offset" initial_value="3.99E-2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_MDH_calculation">
<eq/>
<ci> V_MDH </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Kcat_MDH </ci>
<ci> ET_MDH </ci>
<ci> fh_a </ci>
<ci> fh_i </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_MAL </ci>
<ci> MAL </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> OAA </ci>
<ci> Ki_OAA </ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<ci> Km_NAD </ci>
<ci> NAD </ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_MAL </ci>
<ci> MAL </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> OAA </ci>
<ci> Ki_OAA </ci>
</apply>
</apply>
<apply>
<divide/>
<ci> Km_NAD </ci>
<ci> NAD </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="fh_a_calculation">
<eq/>
<ci> fh_a </ci>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> H </ci>
<ci> kh1 </ci>
</apply>
<apply>
<divide/>
<apply>
<power/>
<ci> H </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<times/>
<ci> kh1 </ci>
<ci> kh2 </ci>
</apply>
</apply>
</apply>
</apply>
<ci> k_offset </ci>
</apply>
</apply>
<apply id="fh_i_calculation">
<eq/>
<ci> fh_i </ci>
<apply>
<power/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> kh3 </ci>
<ci> H </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> kh3 </ci>
<ci> kh4 </ci>
</apply>
<apply>
<power/>
<ci> H </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</math>
</component>
<component name="V_FH">
<variable units="flux" public_interface="out" name="V_FH"/>
<variable units="millimolar" public_interface="in" name="MAL"/>
<variable units="millimolar" public_interface="in" name="FUM"/>
<variable units="dimensionless" name="Ke_FH" initial_value="1.0"/>
<variable units="first_order_rate_constant" name="kf_FH" initial_value="0.83"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_FH_calculation">
<eq/>
<ci> V_FH </ci>
<apply>
<times/>
<ci> kf_FH </ci>
<apply>
<minus/>
<ci> FUM </ci>
<apply>
<divide/>
<ci> MAL </ci>
<ci> Ke_FH </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_AAT">
<variable units="flux" public_interface="out" name="V_AAT"/>
<variable units="millimolar" public_interface="in" name="OAA"/>
<variable units="millimolar" public_interface="in" name="GLU"/>
<variable units="millimolar" public_interface="in" name="ASP"/>
<variable units="millimolar" public_interface="in" name="alpha_KG"/>
<variable units="dimensionless" name="Ke_AAT" initial_value="6.6"/>
<variable units="second_order_rate_constant" name="kf_AAT" initial_value="0.644"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_AAT_calculation">
<eq/>
<ci> V_AAT </ci>
<apply>
<times/>
<ci> kf_AAT </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> OAA </ci>
<ci> GLU </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> alpha_KG </ci>
<ci> ASP </ci>
</apply>
<ci> Ke_AAT </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_C_ASP">
<variable units="flux" public_interface="out" name="V_C_ASP"/>
<variable units="millimolar" public_interface="in" name="ASP"/>
<variable units="first_order_rate_constant" name="k_C_ASP" initial_value="0.01"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_C_ASP_calculation">
<eq/>
<ci> V_C_ASP </ci>
<apply>
<times/>
<ci> k_C_ASP </ci>
<ci> ASP </ci>
</apply>
</apply>
</math>
</component>
<component name="V_SOD" cmeta:id="V_SOD">
<rdf:RDF>
<rdf:Description rdf:about="#V_SOD">
<dc:title>V_SOD</dc:title>
<dcterms:alternative>superoxide dismutase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="V_SOD"/>
<variable units="second_order_rate_constant" name="k1_SOD" initial_value="2.4E6"/>
<variable units="second_order_rate_constant" name="k3_SOD" initial_value="4.8E4"/>
<variable units="first_order_rate_constant" name="k5_SOD" initial_value="5.0E-1"/>
<variable units="millimolar" name="ET_SOD" initial_value="0.4E-3"/>
<variable units="millimolar" name="Ki_H2O2" initial_value="0.5"/>
<variable units="millimolar" public_interface="in" name="O2_i"/>
<variable units="millimolar" public_interface="in" name="H2O2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> V_SOD </ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> k1_SOD </ci>
<ci> k5_SOD </ci>
<apply>
<plus/>
<ci> k1_SOD </ci>
<apply>
<times/>
<ci> k3_SOD </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> H2O2 </ci>
<ci> Ki_H2O2 </ci>
</apply>
</apply>
</apply>
</apply>
<ci> ET_SOD </ci>
<ci> O2_i </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k5_SOD </ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> k1_SOD </ci>
</apply>
<apply>
<times/>
<ci> k3_SOD </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> H2O2 </ci>
<ci> Ki_H2O2 </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> O2_i </ci>
<ci> k1_SOD </ci>
<ci> k3_SOD </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> H2O2 </ci>
<ci> Ki_H2O2 </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_CAT" cmeta:id="V_CAT">
<rdf:RDF>
<rdf:Description rdf:about="#V_CAT">
<dc:title>V_CAT</dc:title>
<dcterms:alternative>Catalase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="V_CAT"/>
<variable units="second_order_rate_constant" name="k1_CAT" initial_value="1.7E4"/>
<variable units="millimolar" name="ET_CAT" initial_value="0.001"/>
<variable units="per_millimolar" name="fr" initial_value="50.0"/>
<variable units="millimolar" public_interface="in" name="H2O2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> V_CAT </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> k1_CAT </ci>
<ci> ET_CAT </ci>
<ci> H2O2 </ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> fr </ci>
</apply>
<ci> H2O2 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_GPX" cmeta:id="V_GPX">
<rdf:RDF>
<rdf:Description rdf:about="#V_GPX">
<dc:title>V_GPX</dc:title>
<dcterms:alternative>Glutathione peroxidase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="V_GPX"/>
<variable units="millimolar_second" name="phi1_GPX" initial_value="0.15"/>
<variable units="millimolar_second" name="phi2_GPX" initial_value="0.5"/>
<variable units="millimolar" name="ET_GPX" initial_value="0.00141"/>
<variable units="millimolar" public_interface="in" name="H2O2"/>
<variable units="millimolar" public_interface="in" name="GSH"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> V_GPX </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> ET_GPX </ci>
<ci> H2O2 </ci>
<ci> GSH </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> phi1_GPX </ci>
<ci> GSH </ci>
</apply>
<apply>
<times/>
<ci> phi2_GPX </ci>
<ci> H2O2 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_GR" cmeta:id="V_GR">
<rdf:RDF>
<rdf:Description rdf:about="#V_GR">
<dc:title>V_GR</dc:title>
<dcterms:alternative>Glutathione reductase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="V_GR"/>
<variable units="first_order_rate_constant" name="k1_GR" initial_value="0.0308"/>
<variable units="millimolar" name="KM_GSSG" initial_value="1.94"/>
<variable units="millimolar" name="KM_NADPH" initial_value="38.7"/>
<variable units="millimolar" name="ET_GR" initial_value="1.27E-3"/>
<variable units="millimolar" public_interface="in" name="NADPH"/>
<variable units="millimolar" public_interface="in" name="GSSG"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> V_GR </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> k1_GR </ci>
<ci> ET_GR </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> KM_GSSG </ci>
<ci> GSSG </ci>
</apply>
<apply>
<divide/>
<ci> KM_NADPH </ci>
<ci> NADPH </ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> KM_GSSG </ci>
<ci> GSSG </ci>
</apply>
<apply>
<divide/>
<ci> KM_NADPH </ci>
<ci> NADPH </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_IMAC" cmeta:id="V_IMAC">
<rdf:RDF>
<rdf:Description rdf:about="#V_IMAC">
<dc:title>V_IMAC</dc:title>
<dcterms:alternative>mitochondrial inner membrane anion channel conductance</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="V_IMAC"/>
<variable units="millimolar_per_second_volt" name="Gmax" initial_value="7.82"/>
<variable units="millimolar_per_second_volt" name="GL" initial_value="0.0782"/>
<variable units="dimensionless" name="a" initial_value="1.0E-3"/>
<variable units="dimensionless" name="b" initial_value="1.0E4"/>
<variable units="per_volt" name="kappa" initial_value="70.0"/>
<variable units="volt" name="delta_psi_bm" initial_value="0.004"/>
<variable units="millimolar" name="Kcc" initial_value="0.01"/>
<variable units="volt" public_interface="in" name="delta_psi_m"/>
<variable units="millimolar" public_interface="in" name="O2_i"/>
<variable units="millimolar" public_interface="in" name="GSSG"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> V_IMAC </ci>
<apply>
<times/>
<apply>
<plus/>
<ci> a </ci>
<apply>
<divide/>
<ci> b </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Kcc </ci>
<ci> O2_i </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci> GL </ci>
<apply>
<divide/>
<ci> Gmax </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<ci> kappa </ci>
<apply>
<minus/>
<ci> delta_psi_bm </ci>
<ci> delta_psi_m </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<ci> delta_psi_m </ci>
</apply>
</apply>
</math>
</component>
<component name="VTr_ROS" cmeta:id="VTr_ROS">
<rdf:RDF>
<rdf:Description rdf:about="#VTr_ROS">
<dc:title>VTr_ROS</dc:title>
<dcterms:alternative>transport of reactive oxygen species across the inner mitochondrial membrane</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="flux" public_interface="out" name="VTr_ROS"/>
<variable units="dimensionless" name="j" initial_value="0.12"/>
<variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="O2_i"/>
<variable units="millimolar" public_interface="in" name="O2_m"/>
<variable units="flux" public_interface="in" name="V_IMAC"/>
<variable units="volt" public_interface="in" name="delta_psi_m"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> VTr_ROS </ci>
<apply>
<times/>
<ci> j </ci>
<apply>
<divide/>
<ci> V_IMAC </ci>
<ci> delta_psi_m </ci>
</apply>
<apply>
<minus/>
<ci> delta_psi_m </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<log/>
<apply>
<divide/>
<ci> O2_m </ci>
<ci> O2_i </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="oxidative_phosphorylation">
<variable units="flux" public_interface="out" name="V_O2"/>
<variable units="flux" public_interface="out" name="V_He"/>
<variable units="flux" public_interface="out" name="V_He_F"/>
<variable units="flux" public_interface="out" name="V_ATPase"/>
<variable units="flux" public_interface="out" name="V_Hu"/>
<variable units="flux" public_interface="out" name="V_Hleak"/>
<variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="NAD"/>
<variable units="millimolar" public_interface="in" name="NADH"/>
<variable units="millimolar" public_interface="in" name="FAD"/>
<variable units="millimolar" public_interface="in" name="FADH2"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<variable units="millimolar" public_interface="in" name="ATP_m"/>
<variable units="millimolar" public_interface="in" name="Pi"/>
<variable units="volt" public_interface="in" name="delta_psi_m"/>
<variable units="millimolar" name="rho_res" initial_value="0.0006"/>
<variable units="millimolar" name="rho_res_F" initial_value="0.0045"/>
<variable units="first_order_rate_constant" name="ra" initial_value="6.394E-10"/>
<variable units="first_order_rate_constant" name="rc1" initial_value="2.656E-19"/>
<variable units="volt" name="Ares"/>
<variable units="volt" name="Ares_F"/>
<variable units="dimensionless" name="r1" initial_value="2.077E-18"/>
<variable units="dimensionless" name="r2" initial_value="1.728E-9"/>
<variable units="dimensionless" name="r3" initial_value="1.059E-26"/>
<variable units="first_order_rate_constant" name="rb" initial_value="1.762E-13"/>
<variable units="first_order_rate_constant" name="rc2" initial_value="8.632E-27"/>
<variable units="dimensionless" name="Kres" initial_value="1.35E18"/>
<variable units="dimensionless" name="Kres_F" initial_value="5.765E13"/>
<variable units="millimolar_per_second_volt" name="gH" initial_value="0.01"/>
<variable units="volt" name="delta_psi_B" initial_value="0.05"/>
<variable units="dimensionless" name="g" initial_value="0.85"/>
<variable units="volt" name="delta_mu_H"/>
<variable units="dimensionless" name="delta_pH" initial_value="-0.6"/>
<variable units="millimolar" name="rho_F1" initial_value="0.06"/>
<variable units="first_order_rate_constant" name="pa" initial_value="1.656E-5"/>
<variable units="first_order_rate_constant" name="pc1" initial_value="9.651E-14"/>
<variable units="volt" name="AF1"/>
<variable units="dimensionless" name="p1" initial_value="1.346E-8"/>
<variable units="dimensionless" name="p2" initial_value="7.739E-7"/>
<variable units="dimensionless" name="p3" initial_value="6.65E-15"/>
<variable units="first_order_rate_constant" name="pb" initial_value="3.373E-7"/>
<variable units="first_order_rate_constant" name="pc2" initial_value="4.585E-14"/>
<variable units="millimolar" name="KF1" initial_value="1.71E6"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_O2_calculation">
<eq/>
<ci> V_O2 </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.5 </cn>
<ci> rho_res </ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> ra </ci>
<apply>
<times/>
<ci> rc1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> Ares </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> ra </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> rc2 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> Ares </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> r1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> r2 </ci>
<apply>
<times/>
<ci> r3 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_He_calculation">
<eq/>
<ci> V_He </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> rho_res </ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> ra </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> ra </ci>
<ci> rb </ci>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> r1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> r2 </ci>
<apply>
<times/>
<ci> r3 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Ares_calculation">
<eq/>
<ci> Ares </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<times/>
<ci> Kres </ci>
<apply>
<power/>
<apply>
<divide/>
<ci> NADH </ci>
<ci> NAD </ci>
</apply>
<cn cellml:units="dimensionless"> 0.5 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_He_F_calculation">
<eq/>
<ci> V_He_F </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> rho_res_F </ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> ra </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares_F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> ra </ci>
<ci> rb </ci>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> r1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares_F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> r2 </ci>
<apply>
<times/>
<ci> r3 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> Ares_F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> g </ci>
<cn cellml:units="dimensionless"> 6.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Ares_F_calculation">
<eq/>
<ci> Ares_F </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<times/>
<ci> Kres_F </ci>
<apply>
<power/>
<apply>
<divide/>
<ci> FADH2 </ci>
<ci> FAD </ci>
</apply>
<cn cellml:units="dimensionless"> 0.5 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_Hleak_calculation">
<eq/>
<ci> V_Hleak </ci>
<apply>
<times/>
<ci> gH </ci>
<ci> delta_mu_H </ci>
</apply>
</apply>
<apply id="delta_mu_H_calculation">
<eq/>
<ci> delta_mu_H </ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<ci> delta_pH </ci>
</apply>
<ci> delta_psi_m </ci>
</apply>
</apply>
<apply id="V_ATPase_calculation">
<eq/>
<ci> V_ATPase </ci>
<apply>
<times/>
<apply>
<minus/>
<ci> rho_F1 </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 100.0 </cn>
<ci> pa </ci>
</apply>
<apply>
<times/>
<ci> pc1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> AF1 </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> pa </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> pc2 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> AF1 </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> p1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> AF1 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> p2 </ci>
<apply>
<times/>
<ci> p3 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> AF1 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_Hu_calculation">
<eq/>
<ci> V_Hu </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> -3.0 </cn>
<ci> rho_F1 </ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 100.0 </cn>
<ci> pa </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> AF1 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> pa </ci>
<ci> pb </ci>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> p1 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> AF1 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_psi_B </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> p2 </ci>
<apply>
<times/>
<ci> p3 </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> F </ci>
<ci> AF1 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 3.0 </cn>
<ci> F </ci>
<ci> delta_mu_H </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="AF1_calculation">
<eq/>
<ci> AF1 </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<times/>
<ci> KF1 </ci>
<apply>
<divide/>
<ci> ATP_m </ci>
<apply>
<times/>
<ci> ADP_m </ci>
<ci> Pi </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_dynamics">
<variable units="flux" public_interface="out" name="V_ANT"/>
<variable units="flux" public_interface="out" name="V_uni"/>
<variable units="flux" public_interface="out" name="V_NaCa"/>
<variable units="millimolar" public_interface="in" name="ADP_i"/>
<variable units="millimolar" public_interface="in" name="ATP_i"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<variable units="millimolar" public_interface="in" name="ATP_m"/>
<variable units="micromolar" public_interface="in" name="Ca_i"/>
<variable units="micromolar" public_interface="in" name="Ca_m"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="volt" public_interface="in" name="delta_psi_m"/>
<variable units="dimensionless" name="h" initial_value="0.5"/>
<variable units="volt" name="delta_psi_0" initial_value="0.091"/>
<variable units="flux" name="Vmax_ANT" initial_value="0.05"/>
<variable units="dimensionless" name="L" initial_value="110.0"/>
<variable units="dimensionless" name="na" initial_value="2.8"/>
<variable units="flux" name="Vmax_uni" initial_value="0.000625"/>
<variable units="micromolar" name="K_act" initial_value="0.38"/>
<variable units="micromolar" name="K_trans" initial_value="19.0"/>
<variable units="dimensionless" name="n" initial_value="3.0"/>
<variable units="flux" name="Vmax_NaCa" initial_value="0.005"/>
<variable units="millimolar" name="KNa" initial_value="9.4"/>
<variable units="micromolar" name="KCa" initial_value="3.75E-1"/>
<variable units="dimensionless" name="b" initial_value="0.5"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V_ANT_calculation">
<eq/>
<ci> V_ANT </ci>
<apply>
<times/>
<ci> Vmax_ANT </ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.05 </cn>
<ci> ATP_i </ci>
<cn cellml:units="dimensionless"> 0.45 </cn>
<cn cellml:units="dimensionless"> 0.8 </cn>
<ci> ADP_m </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.45 </cn>
<ci> ADP_i </ci>
<cn cellml:units="dimensionless"> 0.05 </cn>
<ci> ATP_m </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.05 </cn>
<ci> ATP_i </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.45 </cn>
<ci> ADP_i </ci>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci> h </ci>
</apply>
<ci> F </ci>
<ci> delta_psi_0 </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.45 </cn>
<cn cellml:units="dimensionless"> 0.8 </cn>
<ci> ADP_m </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.05 </cn>
<ci> ATP_m </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_uni_calculation">
<eq/>
<ci> V_uni </ci>
<apply>
<times/>
<ci> Vmax_uni </ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> K_trans </ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> K_trans </ci>
</apply>
</apply>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> F </ci>
<apply>
<minus/>
<ci> delta_psi_m </ci>
<ci> delta_psi_0 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> K_trans </ci>
</apply>
</apply>
<cn cellml:units="dimensionless"> 4.0 </cn>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> L </ci>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> K_act </ci>
</apply>
</apply>
<ci> na </ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> -2.0 </cn>
<ci> F </ci>
<apply>
<minus/>
<ci> delta_psi_m </ci>
<ci> delta_psi_0 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_NaCa_calculation">
<eq/>
<ci> V_NaCa </ci>
<apply>
<times/>
<ci> Vmax_NaCa </ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci> b </ci>
<ci> F </ci>
<apply>
<minus/>
<ci> delta_psi_m </ci>
<ci> delta_psi_0 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<ln/>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> Ca_m </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> KNa </ci>
<ci> Na_i </ci>
</apply>
</apply>
<ci> n </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> KCa </ci>
<ci> Ca_m </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="oxidative_phosphorylation" component_1="ADP_m"/>
<map_variables variable_2="ADP_m" variable_1="ADP_m"/>
<map_variables variable_2="V_ATPase" variable_1="V_ATPase"/>
</connection>
<connection>
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<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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<rdf:value>Added initial conditions for the metabolites. Added a concentration for GLU (glutamate) - this is temporary until the model author confirms the value they used in the original model. Added a value for "ni" in V_IDH (again this is temporary until the model author confirms the value they used in the original model). Kf_AAT is 2nd order not 1st order (in order to balance units). Similarly, Ke_SL and KF1 are mM not dimensionless in order to balance the units.
Also added a component for NADPH as it is required in the equation for V_CAT (we are awaiting confirmation from the model author for the actual concentration of this variable). "fr" in V_CAT was changed from dimensionless to mM-1 in order to balance the units.</rdf:value>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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<dc:title>A mitochondrial oscillator dependent on reactive oxygen species</dc:title>
<bqs:volume>87</bqs:volume>
<bqs:first_page>2060</bqs:first_page>
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<bqs:last_page>2073</bqs:last_page>
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<vCard:Given>Raimond</vCard:Given>
<vCard:Family>Winslow</vCard:Family>
<vCard:Other>L</vCard:Other>
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<dcterms:W3CDTF>2004-09-28T00:00:00+00:00</dcterms:W3CDTF>
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